目的 研究羟丙基甲基纤维素(HPMC)亲水凝胶对托拉塞米渗透的影响.方法 以HPMC为亲水凝胶的辅料,托拉塞米为模型药物,采用三室渗透装置测定药物透过中间室的速度,实验温度为37 ℃,测定时间为1、3、7、10、24 h,考察HPMC的不同质量浓度、黏度对药物渗透速度的影响,与药物本身的渗透速度比较计算阻滞率.结果 半透膜本身对药物的平衡速度有一定影响,37 ℃下10 h透过率约50%,24 h基本达到平衡药物.在HPMC凝胶的存在下,阻滞率随着测定时间的延长而逐步减少,7 h后趋于平缓.HPMC的质量浓度越大对药物的阻滞率越大,黏度升高则阻滞率增加.合理的测定条件为HPMC K100M质量浓度分别为5、10、20 mg/mL,托拉塞米质量浓度为50 μg/mL,在37 ℃水浴条件下,测定时间为10 h.相同型号(100M)的进口与国产HPMC在10、5 mg/mL时阻滞率基本一致,但在20 mg/mL时,国产HPMC的阻滞率明显大于进口产品.结论 HPMC溶胀形成的凝胶层对托拉塞米的渗透具有阻滞作用,对HPMC应用到缓释骨架片的研究提供参考.

Objective To study the effect of hydroxypropyl methyl cellulose (HPMC) hydrogel on penetrability of torasemide. Methods HPMC was prepared into hydrophilic gel, and torasemide was used as representative drug. A device with three compartments was used to determine penetration speed of drug through the middle chamber. Penetration of drug through hydrophilic gel was tested at 1, 3, 7, 10, and 24 h under 37 ℃. The influences of concentration and viscosity of HPMC on penetration speed were taken into consideration. Block rate was calculated by the penetration speed of drug itself. Results Semipermeable membrane had influence on the balance speed of the drug. Under 37 ℃, the penetrated drug molecules was about 50% at 10 h, and the system achieves balance at 24 h. In the presence of the gel, block rate reduced gradually with the time increasing, became flat after 7 h. The higher concentrations of HPMC, the larger block rates of the drug. And the lager viscosities, the larger block rates of the drug. The reasonable standardized condition was as following: 37 ℃ water bath, the concentrations of HPMC were 5, 10, and 20 mg/mL, the concentration of torasemide was 50 μg/mL, and those were determined at 10 h. The same type (100 M) of domestic and imported HPMC was compared to find their difference. Their block rates were similar at 10 mg/mL and 5 mg/mL. But the block rate of domestic product was significantly greater than that of imported product at high concentration. Conclusion HPMC hydrogel has blocking effect on penetrability of torasemide which may provide references on sustained release matrix tablets prepared by HPMC.

天津市应用基础与前沿技术研究计划项目(13JCZDJ28500)